Is heparin administration necessary during induction chemotherapy for patients with acute promyelocytic leukemia?

Abstract

The role of heparin in the treatment of the disseminated intravascular coagulation (DIC) associated with acute promyelocytic leukemia (APL) remains unclear. Between 1974 and 1985, we treated 27 patients with APL using four different chemotherapeutic regimens; 23/27 (85%) had evidence of DIC either at presentation or following the initiation of induction chemotherapy. The coagulopathy was treated primarily with fresh frozen plasma and platelet transfusions; only 2/27 (7%) patients received heparin. Twenty of 27 patients (74%) entered complete remission. Major bleeding or thrombotic complications occurred in 5/27 patients (19%), but 2 of these 5 patients presented after hemorrhage had already occurred. None of the 5 patients with bleeding or thrombosis entered complete remission. All of the hemorrhagic complications due to DIC in our study occurred before 1979, which may reflect changes in the management of leukemic patients. This observation emphasizes the risks inherent in the use of historical controls in this population. In conclusion the DIC associated with APL can be successfully treated with intensive blood product support without the use of heparin.

Acute Promyelocytic Leukemia: A History over 60 Years—From the Most Malignant to the most Curable Form of Acute Leukemia

“…Despite a significant improvement in outcome, the median duration of remission ranged from 11 to 24 months with a 5-year disease-free survival (DFS) of only 35-45% in patients treated by chemotherapy alone (Table 1) [25,29,[37][38][39][40][41][42][43]. The early mortality rate was approximately 15% and the resistant rate was 10%.…”

Bleeding and thrombosis in acute promyelocytic leukemia

“…Heparin has been thought to control the coagulopathy associated with APL by inhibiting intravascular fibrin formation and reducing the consumption of clotting factors and platelets, thereby decreasing the bleeding tendency [19]. There was controversy as to whether heparin improves survival, increases remission rates, or decreases the incidence of CNS bleeding [34, 88–94]. These older therapeutic trials were conducted before the routine introduction of ATRA in the induction therapy of APL, enrolled only small numbers of patients, were not prospective or randomized, and lacked adequate controls.…”

Global Fibrinolytic Capacity in Colorectal Cancer: A New Clue to Occult Fibrinolysis

“…Interacting and counteracting mechanisms of coagulation and fibrinolysis bring out different states of hemostatic imbalance in accord to type and extend of tumor, treatment modalities, and accompanying complications. Catabolism of fibrinogen and platelets is increased in disseminated malignancies as evidenced by increased levels of fibrin degredation products, D-dimer, prothrombin fragment 1 + 2, fibrinopeptide A and B, cryoglobulins, fibrin monomer, platelet factor 4, beta thromboglobulin, fibronectin, and antithrombin (2,(12)(13)(14)(15)(16)(17)(18)(19). A low-grade disseminated intravascular coagulation is present in a significant percentage of cancer patients.…”